Background. Most gastric cancers in the world are attributed to Helicobacter pylori (H. pylori) infections. The prevalence of H. pylori infection is influenced by socioeconomic status, hygiene, and lifestyle of the population. This study aimed to assess sero- and feco-prevalence of H. pylori infections and its associated risk factors among adult dyspeptic patients visiting the outpatient department of Adet Primary Hospital, Yilmana Densa District, northwest Ethiopia. Methods. A hospital-based cross-sectional study was conducted from February 10, 2022 to April 10, 2022. The study participants were selected using a systematic random sampling technique. The data were collected by pretested questionnaires. Blood and stool specimens were collected from each patient for antibody and H. pylori antigen tests, respectively. The data were analyzed using Statistical Package for Social Science (SPSS) version 26.0. A logistic regression model was used to assess the strength of association between H. pylori positivity and risk factors. Results. The sero- and feco-prevalence of H. pylori infection was 62% and 51.1%, respectively. In those patients who had a positive result with either the antibody (Ab) or antigen (Ag) test, rural residence (AOR = 5.55; 95% CI: 2.34–13.14;
p
<
0.001
), alcohol consumption (AOR = 12.34; 95% CI: 2.29–66.51;
p
=
0.003
), having no awareness about H. pylori transmission (AOR = 4.76; 95% CI: 1.86–12.15;
p
=
0.001
), using pond/river as a source of drinking water (AOR = 5.22; 95% CI: 1.91–14.27;
p
=
0.001
), and open field defecation (AOR = 4.19; 95% CI: 1.67–10.52;
p
=
0.002
) were the explanatory risk factors significantly associated with H. pylori infection. Conclusion. This study showed that the prevalence of H. pylori infection was very high. Most cases of gastric cancers are ascribed to H. pylori infection. Therefore, education should be given to communities so as to increase their awareness of the infection and the associated major explanatory risk factors identified in the present study.